Novel Association between Opioid Use and Increased Risk of Retinal Vein Occlusion Using the National Institutes of Health All of Us Research Program.

Purpose: To assess for risk factors for retinal vein occlusion (RVO) among participants in the National Institutes of Health All of Us database, particularly social risk factors that have not been well studied, including substance use. Design: Retrospective, case-control study. Participants: Data were extracted for 380 adult participants with branch retinal vein occlusion (BRVO), 311 adult participants with central retinal vein occlusion (CRVO), and 1520 controls sampled among 311 640 adult participants in the All of Us database. Methods: Data were extracted regarding demographics, comorbidities, income, housing, insurance, and substance use. Opioid use was defined by relevant diagnosis and prescription codes, with prescription use > 30 days. Controls were sampled at a 4:1 control to case ratio from a pool of individuals aged > 18 years without a diagnosis of RVO and proportionally matched to the demographic distribution of the 2019 U.S. census. Multivariable logistic regression identified medical and social determinants significantly associated with BRVO or CRVO. Statistical significance was defined as P < 0.05. Main Outcome Measure: Development of BRVO or CRVO based on diagnosis codes. Results: Among patients with BRVO, the mean (standard deviation) age was 70.1 (10.5) years. The majority (53.7%) were female. Cases were diverse; 23.7% identified as Black, and 18.4% identified as Hispanic or Latino. Medical risk factors including glaucoma (odds ratio [OR], 3.29; 95% confidence interval [CI], 2.22-4.90; P < 0.001), hypertension (OR, 2.15; 95% CI, 1.49-3.11; P < 0.001), and diabetes mellitus (OR, 1.68; 95% CI, 1.18-2.38; P = 0.004) were re-demonstrated to be associated with BRVO. Black race (OR, 2.64; 95% CI, 1.22-6.05; P = 0.017) was found to be associated with increased risk of BRVO. Past marijuana use (OR, 0.68; 95% CI, 0.50-0.92; P = 0.013) was associated with decreased risk of BRVO; however, opioid use (OR, 1.98; 95% CI, 1.41-2.78; P < 0.001) was associated with a significantly increased risk of BRVO. Similar associations were found for CRVO. Conclusions: Understanding RVO risk factors is important for primary prevention and improvement in visual outcomes. This study capitalizes on the diversity and scale of a novel nationwide database to elucidate a previously uncharacterized association between RVO and opioid use.